Proteomics

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ITARGEX analysis of yeast deletome reveals novel regulators of transcriptional buffering in S phase and protein turnover


ABSTRACT: Integrating omics data with quantification of biological traits provides unparalleled opportunities for discovery of genetic regulators by in silico inference. However, current approaches to analyze genetic-perturbation screens are limited by their reliance on annotation libraries for prioritization of hits and subsequent targeted experimentation. Here, we present iTARGEX (identification of Trait-Associated Regulatory Genes via mixture regression using EXpectation maximization), an association framework with no requirement of a priori knowledge of gene function. After creating this tool, we used it to test associations between gene expression profiles and two biological traits in single-gene-deleted budding yeast mutants, including transcription homeostasis during S phase and global protein turnover. For each trait, we discovered novel regulators without prior functional annotations. The functional effects of the novel candidates were then validated experimentally, providing solid evidence for their roles in the respective traits. Hence, we conclude that iTARGEX can reliably identify novel factors involved in given biological traits. As such, it is capable of converting genome-wide observations into causal gene function predictions. Further application of iTARGEX in other contexts is expected to facilitate the discovery of new regulators and provide observations for novel mechanistic hypotheses regarding different biological traits and phenotypes.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

SUBMITTER: Cheng-Fu Kao  

LAB HEAD: Cheng-Fu Kao

PROVIDER: PXD024258 | Pride | 2021-09-10

REPOSITORIES: Pride

Dataset's files

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Publications

iTARGEX analysis of yeast deletome reveals novel regulators of transcriptional buffering in S phase and protein turnover.

Huang Jia-Hsin JH   Liao You-Rou YR   Lin Tzu-Chieh TC   Tsai Cheng-Hung CH   Lai Wei-Yun WY   Chou Yang-Kai YK   Leu Jun-Yi JY   Tsai Huai-Kuang HK   Kao Cheng-Fu CF  

Nucleic acids research 20210701 13


Integrating omics data with quantification of biological traits provides unparalleled opportunities for discovery of genetic regulators by in silico inference. However, current approaches to analyze genetic-perturbation screens are limited by their reliance on annotation libraries for prioritization of hits and subsequent targeted experimentation. Here, we present iTARGEX (identification of Trait-Associated Regulatory Genes via mixture regression using EXpectation maximization), an association f  ...[more]

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